This Biomedical Research Partnership proposal represents a multidisciplinary approach to advance the state of the art in diagnostic anatomical and functional imaging in situ at the micron scale. This will be achieved by developing fundamental advances in the technology of Optical Coherence Tomography, validating new techniques using animal models, and employing new technologies in pilot clinical studies. The Partnership includes biomedical engineers and clinicians from five institutions with demonstrated leadership in the transfer of optical diagnostic technologies to clinical practice. The specific aims of the proposal and the institutions involved in each (abbreviations found below) are: 1. To enhance and expand the clinical utility of Optical Coherence Tomography by developing the following core technologies: I) high frame rate imaging, ii) ultrahigh resolution imaging, iii) minimally invasive endoscopic and ophthalmic delivery systems, and iv) imaging of physiological function including blood flow and tissue hydration (CWRU-BME). 2. To apply these technologies for pilot studies of early cancer detection in the gastrointestinal tract (CWRU MED, CWRU-BME). 3. To apply these technologies for studies of chemoprevention and early cancer detection in the lung (BCCA, CWRU-BME). 4. To improve the accuracy and safety of keratorefractive surgery by developing OCT technology to measure the corneal epithelial remodeling response, structural stability, and hydration changes following laser in-situ keratomileusis (LASIK) (CCFEI), CWRU-BME). 5. To improve imaging of retinal, sub-retinal, and vitreous pathologies with increased resolution and reduced motion artifacts (CCFEI, DUEC,CWRU-BME). 6. To apply functional imaging technologies for the quantitative detection of retinal/choroidal blood flow and vitreoretinal strand motion in animals and humans, and to apply these technologies to monitor patients with vascular complications of diabetes, glaucoma, age related macular degeneration, and retinal occlusive disease (NU, CCF, DUEC, CWRU-BME); and patients with vitreomacular interface abnormalities (DUEC). By the end of the first year of the project, all Partners will have state of the art faciliti4es for optical coherence tomography research and will be engaged in in vitro or in vivo studies related to endoscopic/bronchosopic cancer imaging or ophthalmic diagnosis. Technical innovations developed at the grantee and Partner institutions will be rapidly shared among the Partnership; clinical study results will lead to a new technology optimization through regular interactions between Partnership personnel.